Field of the Invention
The present invention relates to bisacodyl compositions, delivery devices, and methods of use as a rectal suppository.
Description of the Related Art
Bisacodyl (4,4′-(pyridin-2-ylmethylene)bis(4,1-phenylene) diacetate) is an organic compound used as a contact laxative drug. Bisacodyl is an inactive prodrug hydrolyzed by intestinal brush border enzymes and colonic bacteria to active desacetyl bisacodyl. Contact of the desacetyl bisacodyl with the mucosa of the colon stimulates sensory nerve endings to produce increased propulsive peristaltic contractions of the colon accelerating movement of contents through the colon. Jauch, et al., Arzneim.-Forsch./Drug Res. 25(11): 1796-1800, 1975. Bisacodyl is used to relieve constipation and for the management of neurogenic bowel dysfunction as well as part of bowel preparation before medical examinations, such as colonoscopy. Wexner, et al. Gastrointestinal Endoscopy 63 (7): 894-909; Robert Engelhorn, Ernst Seeger and Jan H. Zwaving “Laxatives” in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2000.
Bisacodyl can be administered orally in a dosage range of 5-10 milligrams and takes 6-12 hours to have an effect. Bisacodyl may be administered rectally in suppository form in a dosage range of 10 mg and is usually effective in 15-60 minutes. Robert Engelhorn, Ernst Seeger and Jan H. Zwaving “Laxatives” in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2000; Kamm, et al., Gut 29: 1085-1092, 1988; Preston & Lennard-Jones Digestive Diseases and Sciences 30(4): 289-294, 1985; Leng-Peschlow Pharmacology 38: 310-318, 1988.
Numerous compositions for oral delivery of bisacodyl are known in the art. Commercially available bisacodyl compositions for oral delivery may be coated with a low level of an enteric polymer or combination of polymers, e.g., Dulcolax® (enteric coated bisacodyl tablets) Dulcolax® is coated with a low level of cellulose acetate phthalate, and each tablet has about 5 mg of bisacodyl.
U.S. Pat. No. 5,171,580 discloses a preparation for delivery in the large intestine and especially the colon, comprising an active containing core coated with three protection layers of coatings having different solubilities. The inner layer is Eudragit® S, with a coating thickness of about 40-120 microns, the intermediate coating layer is a swellable polymer with a coating thickness of about 40-120 microns, and the outer layer is cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, polyvinyl acetate phthalate, hydroxyethyl cellulose phthalate, cellulose acetate tetrahydrophthalate, or Eudragit® L.
U.S. Pat. No. 4,910,021 discloses a targeted delivery system wherein the composition comprises a hard or soft gelatin capsule containing an active ingredient such as insulin and an absorption promoter which is coated with a film forming composition being sufficiently soluble at a pH above 7 as to be capable of permitting the erosion or dissolution of the capsule. The film forming composition is a mixture of Eudragit® L, Eudragit® S, and Eudragit® S at specific ratios to provide solubility above a pH of 7.
U.S. Pat. No. 4,432,966 discloses a compressed tablet with an active agent, coated with a first coating layer comprising a mixture of microcrystalline cellulose and lower alkyl ether of a cellulose film-forming organic polymer such as ethyl cellulose, and a second coating layer selected from cellulose acetylphthalate, hydroxypropyl methylcellulose phthalate, benzophenyl salicylate, cellulose acetosuccinate, copolymers of styrene and of malcic acid, formulated gelatin, salol, keratin, steraric acid, myristic acid, gluten, acrylic and methacrylic resins, and copolymers of maleic acid and phthalic acid derivatives.
U.S. Pat. No. 5,330,759 discloses soft capsules coated with an enteric coating comprising from about 1 to about 20 mg/cm2 of 1:1 copolymer of methacrylic acid and methyl or ethyl acrylate or methyl ethyl methacrylate and a plasticizer.
U.S. Pat. No. 7,704,948 discloses a pharmaceutical composition comprising poloxamer and bisacodyl, wherein the bisacodyl in a single dosage form is coated with an enteric coat, and a protective overcoat is coated on the enteric coat to stabilize the enteric coat from plasticization by the poloxamer, where the enteric coat and the protective overcoat separate poloxamer from the bisacodyl.
WO 1994/018973 discloses a pharmaceutical composition in dosage unit form for per oral administration of bisacodyl to a human or lower animal having a gastrointestinal tract, with a lumen there through, with a small intestine and a colon with a junction there between, comprising: (a) an amount of rapidly-dissolving bisacodyl means; and (b) a delivery means which prevents the release of bisacodyl from the dosage form into the lumen of the gastrointestinal tract during transport of the dosage form through the lumen until the dosage form is near the junction between the small intestine and the colon or in the colon, and which then releases the bisacodyl in the lumen near the junction between the small intestine and the colon or within the colon.
U.S. Pat. No. 5,670,158 discloses a pharmaceutical composition in dosage unit form, for per oral administration of bisacodyl.
U.S. Pat. No. 5,068,110 discloses dosage forms with a high level of enteric coating using aqueous systems in their manufacturer, such as Eudragit® L30D, Aquatic® (cellulose acetate phthalate) and Coat Erie® (polyvinyl acetate phthalate), for improved dissolution stability for storage under high stress conditions. The coating levels disclosed are from 14-24 mg/cm2, of a single layer of one enteric polymer. These dosage forms are delivered to the small intestine as opposed to the colon.
Bisacodyl may also be administered rectally for delivery directly to the colon. U.S. Pat. No. 5,656,290 discloses spherical unit dosage forms containing bisacodyl for colonic delivery to provide laxation in the colon.
C.B. Fleet Company, Incorporated sells a bisacodyl suspension product at a concentration of 0.033% bisacodyl packaged in a 1.25 ounce polyethylene squeeze bottle containing 37 mL of FLEET® Bisacodyl Enema product. The FLEET® Bisacodyl Enema product has an average shelf-life of less than 18 months.
Flexible tubes for packaging foodstuffs and a small portion of pharmaceutically products are known in the art, but such packaging has not been known for use in dispensing for rectal administration.
U.S. Pat. No. 8,377,532 discloses aluminum barrier laminates for use as flexible tube packaging for foodstuffs, such as those manufactured by Huhtamaki, which can be in contact with foodstuffs.
U.S. Patent Application Pub. No. 2012/0010060 discloses a laminate film with at least one barrier layer that may be sterilized. The film layers disclosed include polypropylene with a thickness of 70 μm, aluminum with a thickness of 8 μm, and polyethylene terephthalate with a thickness of 12 μm. A method of making the laminate film is also disclosed.